MLLr leukemia exhibits an aberrant enhancer landscape. (A) PCA using all enhancers classifies normal (green) and tumors (red and orange) into distinct clusters. (B) Pie chart showing the gained (15 189), shared (3508), and lost (1504) enhancers in MLLr leukemia. (C) H3K27ac enrichment at gained enhancers in MLLr leukemia. Averaged profiles of the H3K27ac ChIP-seq signal at enhancers in healthy and tumor samples (top). Heatmap plots of the H3K27ac ChIP-seq signal at enhancers in healthy and tumor samples (bottom). (D) Meta tracks of histone modification signals across tumor-specific enhancers. Candidate gene expression is shown to the right of each track. Enhancer region is highlighted with red box. (E) Top enriched gene ontology terms for enhancer associated genes in tumor cells determined by querying the Molecular Signatures Database (MSigDB) Perturbation gene sets. (F,G) GSEA using gene sets for AML and myeloid cell development, comparing the expression of genes associated with gained enhancers in tumor vs normal. FDR, false discovery rate; NES, normalized enrichment score.